Ruan Liancheng, Ma Xiong, Zhu Lingxiao, Su Lang, Wang Silin, Guo Qiang, Wan Bingen, Qiu Shengyu, Zhang Yang, Hu Sheng, Zhou Binfeng, Wei Yiping
Department of Thoracic Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China.
Department of Thoracic Surgery, People's Hospital of Yingtan, Yingtan, China.
J Thorac Dis. 2024 Sep 30;16(9):5559-5570. doi: 10.21037/jtd-24-798. Epub 2024 Sep 13.
Spontaneous pneumothorax (SP) is a common pleural disease in adolescents and adults. However, the role of immunological characteristics in the pathogenesis of SP remains unclear. This study aims to clarify the causal associations between circulating immune cells, lymphocyte subgroups, and SP susceptibility.
Employing Mendelian randomization (MR), the causal association between circulating immune blood cells and lymphocyte subgroups on SP susceptibility have been assessed. Reverse MR analysis was used to further explore the causal relationship. The MR analysis ensured the reliability of the study results through the deletion of confounding single nucleotide polymorphisms (SNPs), heterogeneity testing, sensitivity analysis.
Seven immune cells and SP risk under stringent and lenient threshold conditions were identified. Eosinophils absolute count (AC) [odds ratio (OR) =1.0014, 95% confidence interval (CI): 1.0001-1.0014, P=0.02], memory B cell %B cell ratio (OR =1.008, 95% CI: 1.0002-1.0015, P=0.01), CD4 T cell AC (OR =1.0014, 95% CI: 1.0003-1.0025, P=0.009), effector memory CD4 T cell %T cell ratio (OR =1.0028, 95% CI: 1.0010-1.0046, P=0.003), and HLA-DRCD8 T cell %T cell ratio (OR =1.0019, 95% CI: 1.0004-1.0035, P=0.01) were identified as risk factors for increased susceptibility to SP. Conversely, CD8dim T cell AC (OR =0.9983, 95% CI: 0.9967-0.9999, P=0.03) and CD8dim natural killer T (NKT) %T cell ratio (OR =0.9982, 95% CI: 0.9965-0.9999, P=0.04) exhibited protective effects on SP. In natural killer (NK) cell subgroups and reverse MR analysis, no significance was found.
This study establishes a close causal relationship between immune cells and SP through genetic methods, providing a new perspective for understanding the pathophysiological mechanisms of SP.
自发性气胸（SP）是青少年和成年人中常见的胸膜疾病。然而，免疫特征在SP发病机制中的作用仍不清楚。本研究旨在阐明循环免疫细胞、淋巴细胞亚群与SP易感性之间的因果关系。
采用孟德尔随机化（MR）方法，评估循环免疫血细胞和淋巴细胞亚群与SP易感性之间的因果关系。采用反向MR分析进一步探讨因果关系。MR分析通过删除混杂单核苷酸多态性（SNP）、异质性检验、敏感性分析确保了研究结果的可靠性。
在严格和宽松阈值条件下，确定了7种免疫细胞与SP风险。嗜酸性粒细胞绝对计数（AC）[比值比（OR）=1.0014，95%置信区间（CI）：1.0001-1.0014，P=0.02]、记忆B细胞%B细胞比例（OR =1.008，95%CI：1.0002-1.0015，P=0.01）、CD4 T细胞AC（OR =1.0014，95%CI：1.0003-1.0025，P=0.009）、效应记忆CD4 T细胞%T细胞比例（OR =1.0028，95%CI：1.0010-1.0046，P=0.003）和HLA-DRCD8 T细胞%T细胞比例（OR =1.0019，95%CI：1.0004-1.0035，P=0.01）被确定为SP易感性增加的危险因素。相反，CD8dim T细胞AC（OR =0.9983，95%CI：0.9967-0.9999，P=0.03）和CD8dim自然杀伤T（NKT）%T细胞比例（OR =0.9982，95%CI：0.9965-0.9999，P=0.04）对SP具有保护作用。在自然杀伤（NK）细胞亚群和反向MR分析中，未发现显著意义。
本研究通过遗传学方法建立了免疫细胞与SP之间的密切因果关系，为理解SP的病理生理机制提供了新的视角。
